Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion.
Green tea polyphenol epigallocatechin-3-gallate suppresses melanoma growth by inhibiting inflammasome and IL-1β secretion.
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DOI：
10.1016/j.bbrc.2011.09.115
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发表时间：
2011-10-28
影响因子：
3.1
通讯作者：
Fujita, Mayumi
中科院分区：
文献类型：
--
作者：
Ellis, Lixia Z.;Liu, Weimin;Luo, Yuchun;Okamoto, Miyako;Qu, Dovina;Dunn, Jeffrey H.;Fujita, Mayumi
表没食子儿茶素没食子酸酯（Epigallocatechin-3-gallate，EGCG）是绿色茶的主要多酚类成分，具有抗炎、抗氧化、抗突变和抗癌等作用。以前已经提出了EGCG的抗黑色素瘤作用，但尚未建立明确的作用机制。在这项研究中，我们证明了EGCG在生理剂量（0.1-1 μM）下抑制黑色素瘤细胞生长。在寻找EGCG介导的黑色素瘤细胞抑制机制时，我们发现NF-κB被抑制，NF-κB活性降低与黑色素瘤细胞分泌IL-1β减少有关。由于炎性小体参与IL-1β的分泌，我们研究了IL-1β的抑制是否由炎性小体介导，并发现EGCG处理导致炎性小体组分NLRP 1的下调，并减少caspase-1的活化。此外，沉默NLRP 1的表达在体外和体内都消除了EGCG诱导的肿瘤细胞增殖抑制，表明炎性小体在EGCG功效中的关键作用。本文提出了EGCG抑制黑色素瘤的新机制：炎性小体下调→ IL-1β分泌减少→ NF-κB活性降低→细胞生长抑制。此外，它表明炎性小体和IL-1β可能是未来黑色素瘤治疗的潜在靶点。
Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green tea, has been demonstrated to possess anti-inflammatory, antioxidant, anti-mutagenic and anti-carcinogenic properties. The anti-melanoma effect of EGCG has been previously suggested, but no clear mechanism of action has been established. In this study, we demonstrated that EGCG inhibits melanoma cell growth at physiological doses (0.1–1 μM). In the search for mechanisms of EGCG-mediated melanoma cell suppression, we found that NF-κB was inhibited, and that reduced NF-κB activity was associated with decreased IL-1β secretion from melanoma cells. Since inflammasomes are involved in IL-1β secretion, we investigated whether IL-1β suppression was mediated by inflammasomes, and found that EGCG treatment led to downregulation of the inflammasome component, NLRP1, and reduced caspase-1 activation. Furthermore, silencing the expression of NLRP1 abolished EGCG-induced inhibition of tumor cell proliferation both in vitro and in vivo, suggesting a key role of inflammasomes in EGCG efficacy. This paper provides a novel mechanism for EGCG-induced melanoma inhibition: inflammasome downregulation → decreased IL-1β secretion → decreased NF-κB activities → decreased cell growth. In addition, it suggests inflammasomes and IL-1β could be potential targets for future melanoma therapeutics.
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影响因子：
3.9
作者：
Lambert JD;Elias RJ
通讯作者：
Elias RJ
影响因子：
11.2
作者：
van Deventer HW;Burgents JE;Wu QP;Woodford RM;Brickey WJ;Allen IC;McElvania-Tekippe E;Serody JS;Ting JP
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作者：
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通讯作者：
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